Primary central nervous system lymphoma (PCNSL) is non-Hodgkin’s lymphoma (NHL) confined to the central nervous system. Most of the patients eventually develop relapsed/refractory (R/R) PCNSL, and the overall prognosis for PCNSL remains dismal. Recently, gene sequencing, transcriptome sequencing, and single-cell sequencing platforms have provided a large amount of data revealing the mechanisms underlying the pathogenesis and drug resistance in PCNSL, including the activation of the NF-κB signaling pathway in tumor cells, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Advances in molecular pathology studies for PCNSL have led to identifying new therapeutic targets and developing novel drugs. New therapeutic strategies, such as creating small molecule targeted agents, immunomodulatory drugs, immune checkpoint inhibitors, and chimeric antigen receptor T (CAR-T) cell therapy, have brought new hope for patients with PCNSL, especially for R/R PCNSL. This review presents recent advances in the treatment of PCNSL, reviews and discusses the efficacy and challenges of targeted therapy and immunotherapy, and provides an outlook on the future development of PCNSL treatment strategies.

BACKGROUND:Glioma, characterized by limited lymphocytic infiltration, constitutes an "immune-desert" tumor displaying insensitivity to various immunotherapies. This study aims to explore therapeutic strategies for inducing tertiary lymphoid structure (TLS) formation within the glioma microenvironment (GME) to transition it from an immune resistant to an activated state. METHODS:TLS formation in GME was successfully induced by intracranial administration of Toll-like receptor (TLR) agonists (OK-432, TLR2/4/9 agonist) and glioma antigens (i.c. αTLR-mix). We employed staining analysis, antibody neutralization, single-cell RNA sequencing (scRNA-Seq), and BCR/TCR sequencing to investigate the underlying mechanisms of TLS formation and its role in anti-glioma immunity. Additionally, a preliminary translational clinical study was conducted. RESULTS:TLS formation correlated with increased lymphocyte infiltration in GME and led to improved prognosis in glioma-bearing mice. In the study of TLS induction mechanisms, certain macrophages/microglia and Th17 displayed markers of "LTo" and "LTi" cells, respectively, interaction through LTα/β-LTβR promoted TLS induction. Post-TLS formation, CD4 + and CD8 + T cells but not CD19 + B cells contributed to anti-glioma immunity. Comparative analysis of B/T cells between brain and lymph node showed that brain B/T cells unveiled the switch from naïve to mature, some B cells highlighted an enrichment of class switch recombination (CSR)-associated genes, V gene usage, and clonotype bias were observed. In related clinical studies, i.c. αTLR-mix treatment exhibited tolerability, and chemokines/cytokines assay provided preliminary evidence supporting TLS formation in GME. CONCLUSIONS:TLS induction in GME enhanced anti-glioma immunity, improved the immune microenvironment, and controlled glioma growth, suggesting potential therapeutic avenues for treating glioma in the future.

This study investigated the role of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2-3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2-3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR >90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2-mutant and 1p/19q non-codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels >20%). Astrocytomas were more common in the low-methylated group (10%-20%), while IDH wild-type gliomas were mostly unmethylated (<10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low-methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low-methylated and unmethylated cases were more likely to invade the temporal-insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal-insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2-3 gliomas, providing insights into why astrocytomas and IDH wild-type lower-grade glioma might derive less benefit from chemotherapy.

A highly immunosuppressive tumor microenvironment (TME) and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma (HGG). Here, we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C) to establish a robust antitumor immune response in this registered clinical trial (NCT03392545). During the follow-up, 12/27 (44.4%) patients who achieved tumor control concomitant with survival benefit were regarded as responders in our study. We found that the T-cell receptor (TCR) repertoire in the TME was reshaped after poly(I:C) treatment. Based on the RNA-seq analysis of tumor samples, the expression of annexin A1 (ANXA1) was significantly upregulated in the tumor cells of nonresponders, which was further validated at the protein level. In vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1 (FPR1) to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(I:C). The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven TME. Moreover, ANXA1 could serve as a reliable predictor of response to poly(I:C), with a notable predictive accuracy rate of 92.3%. In light of these notable findings, this study unveils a new perspective of immunotherapy for gliomas.

BACKGROUND:Macrophages play an important role in maintaining the chronic inflammatory of atherosclerosis (AS) and are hallmark of atherosclerotic plaques. They differentiate into different subpopulations under the influence of oxidized lipids and cytokines and play different roles in the formation and development of plaque. To explore the differences in the amount and distribution of different macrophage subpopulations around different carotid plaque pathological features in human AS, and based on these results, to explore the correlation between some macrophage subpopulations and AS pathological features.METHODS:First, we analyzed the single cells RNA-sequence data from the Gene Expression Omnibus DataSets (GSE159677). Second, we investigated the distribution difference of macrophage subpopulations in 61 surgically resected AS plaques by markers staining include CD68, inducible nitric oxide synthase, Arg-1, CD163 and HO-1.RESULTS:The result of single cells RNA-Sequence analysis showed that there were a large number of macrophages infiltrated in AS and they can be categorized into different subpopulations with different transcriptional features and functions; moreover in different part of AS (calcified AS core versus proximal adjacent), the total number and subpopulation ratios were all different. The result of staining analysis showed that macrophages mainly distributed in some pathological lesions such as necrosis, fibrous tissue degeneration, cholesterol crystallization etc., and different subpopulations were distributed differently in these lesions.CONCLUSIONS:This study confirmed that macrophages were heavily infiltrated in atherosclerotic plaques, and there existed subtype variability in different pathological lesions; meanwhile, these results suggested that different macrophage subpopulations may contribute differently in different pathological lesions.

OBJECTIVE:Calcification is a hallmark characteristic of oligodendroglioma (ODG) that may be used as a diagnostic factor, but its prognostic implications remain unclear. This study aimed to investigate the features of calcified ODGs and to evaluate the differences in survival between patients with calcified and noncalcified ODGs.METHODS:We retrospectively reviewed the records of 305 consecutive patients who were diagnosed with IDH-mutant, 1p/19q codeleted ODG at our institution from July 2009 to August 2020. Patients with intratumoral calcification were identified. The clinical, radiologic, and molecular features of the patients in the calcified group and noncalcified group were recorded. Univariate and multivariate analyses were performed to identify prognostic factors.RESULTS:Of the 305 patients, 112 (36.7%) were confirmed to have intratumoral calcification. Compared to ODGs without calcification, ODGs with calcifications had a larger tumor diameter; lower degree of resection; higher tumor grade; higher MGMT methylation level; higher Ki-67 index; and higher rates of midline crossing, enhancement, cyst, and 1q/19p copolysomy, and patients with calcification were more likely to receive chemoradiotherapy. ODGs with T2 hypointense calcification had a higher Hounsfield unit (HU) value on CT scans, and a lower degree of resection. Patients with T2 hypointense calcification ODGs had a shorter survival than those with non-hypointense calcification ODGs. ODGs with calcification and cysts showed a higher Ki-67 index, tumor grade, and enhanced rate, and the patients had an unfavorable overall survival (OS). Calcification was found to be a negative prognostic factor for both progression-free survival (PFS) and OS by univariate analysis, which was confirmed by the Cox proportional hazard model.CONCLUSIONS:Calcification is a useful negative prognostic factor for PFS and OS in patients with ODGs and could therefore be helpful in guiding personalized treatment and predicting patient prognosis.CLINICAL RELEVANCE STATEMENT:Calcification can serve as an independent prognostic factor for patients with oligodendroglioma and shows a vital role in guiding individualized treatment.KEY POINTS:• Intratumoral calcification is an independent negative prognostic risk factor for progression-free survival and overall survival in oligodendroglioma patients. • Calcifications in oligodendroglioma can be divided into hypointense and non-hypointense subtypes based on T2-weighted imaging, and patients with T2-hypointense calcification oligodendrogliomas have worse prognosis. • Calcification concurrent with cysts indicates a more aggressive phenotype of oligodendrogliomas and a significantly reduced survival rate.

Malignant transformation (MT) of low-grade gliomas (LGGs) to a higher-grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2-2 (n = 81, 35.4%), group 2-3 (n = 91, 39.7%), and group 2-4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki-67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post-progression enhancement (PPE) compared with those in group 2-2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2-2 had the longest survival, followed by group 2-3 and then group 2-4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.

Background Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) is an intractable situation without sound treatment. Bruton’s tyrosine kinase (BTK) represents an attractive drug target in PCNSL. Orelabrutinib is a new-generation BTK inhibitor with high cerebrospinal fluid (CSF) concentration. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing combination therapy in patients with r/r PCNSL. Methods We retrospectively analyzed r/r PCNSL patients who received combination therapy with rituximab, high-dose methotrexate, temozolomide, orelabrutinib and lenalidomide, and further explored the relationship between the efficacy and genetic characteristics. Results A total of fifteen patients were included in this retrospective study. The overall response rate (ORR) was 86.7%, the complete remission (CR) rate was 73.3% and the disease control rate (DCR) was 93.3%. Among 13 responders, 9 patients are still receiving oral orelabrutinib and lenalidomide. The most common adverse event (AEs) was transaminase increase (66.7%). No grade 4 AE or drug-related death was reported. Genomic sequencing showed that patients who responded to orelabrutinib had abnormal NF-κB activation, while those who had no response were mainly enriched with transcriptional misregulation. Patients who had mutations in TLR, BCR, or NF-κB pathway achieved complete or partial response to the orelabrutinib-containing therapy. Moreover, the blood and cerebrospinal fluid circulating tumor DNA (ctDNA) were closely associated with tumor recurrence and treatment response and sustained tumor responses correlated with the clearance of ctDNA. Conclusion Orelabrutinib-containing regimen was effective and well-tolerated in patients with r/r PCNSL. Genome sequencing of tumor samples could help to screen patients who may respond to the orelabrutinib-containing regimen, and liquid biopsy may contribute to tracing tumor burden and monitoring treatment response.

Purpose Newly emerged or constantly enlarged contrast-enhancing (CE) lesions were the necessary signs for the diagnosis of glioblastoma (GBM) progression. This study aimed to investigate whether the T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) abnormal transformation could predict and assess progression for GBMs, especially for tumor dissemination. Methods A consecutive cohort of 246 GBM patients with regular follow-up and sufficient radiological data was included in this study. The series of T2/FLAIR and T1CE images were retrospectively reviewed. The patients were separated into T2/FLAIR and T1CE discordant and accordant subgroups based on the initial progression images. Results A total of 170 qualified patients were finally analyzed. The incidence of discordant T2/FLAIR and T1CE images was 25.9% (44/170). The median time-span of T2/FLAIR indicated tumor progression was 119.5 days (ranging from 57 days-unreached) prior to T1CE. Nearly half of patients (20/44, 45.5%) in the discordant subgroup suffered from tumor dissemination, substantially higher than accordant patients (23/126, 20.6%, p < 0.001). The median time to progression (TTP), post-progression survival (PPS), and overall survival (OS) were not statistically different (all p > 0.05) between discordant and accordant patients. Conclusions T2/FLAIR abnormity could be the sign of GBM progression, especially for newly emerged lesions disseminating from the primary cavity. Physicians should cast more attention on the dynamic change of T2/FLAIR images, which might be of great significance for progression assessment and subsequent clinical decision-making.

BackgroundThe diagnosis of oligodendroglioma based on the latest World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS 5) criteria requires the codeletion of chromosome arms 1p and 19q and isocitrate dehydrogenase gene (IDH) mutation (mut). Previously identified prognostic indicators may not be completely suitable for patients with oligodendroglioma based on the new diagnostic criteria. To find potential prognostic indicators for oligodendroglioma, we analyzed the expression of mRNAs of oligodendrogliomas in Chinese Glioma Genome Atlas (CGGA).MethodsWe collected 165 CGGA oligodendroglioma mRNA-sequence datasets and divided them into two cohorts. Patients in the two cohorts were further classified into long-survival and short-survival subgroups. The most predictive mRNAs were filtered out of differentially expressed mRNAs (DE mRNAs) between long-survival and short-survival patients in the training cohort by least absolute shrinkage and selection operator (LASSO), and risk scores of patients were calculated. Univariate and multivariate analyses were performed to screen factors associated with survival and establish the prognostic model. qRT-PCR was used to validate the expression differences of mRNAs.ResultsA total of 88 DE mRNAs were identified between the long-survival and the short-survival groups in the training cohort. Seven RNAs were selected to calculate risk scores. Univariate analysis showed that risk level, age, and primary-or-recurrent status (PRS) type were statistically correlated with survival and were used as factors to establish a prognostic model for patients with oligodendroglioma. The model showed an optimal predictive accuracy with a C-index of 0.912 (95% CI, 0.679–0.981) and harbored a good agreement between the predictions and observations in both training and validation cohorts.ConclusionWe established a prognostic model based on mRNA-sequence data for patients with oligodendroglioma. The predictive ability of this model was validated in a validation cohort, which demonstrated optimal accuracy. The 7 mRNAs included in the model would help predict the prognosis of patients and guide personalized treatment.

Objective:To investigate the diagnostic significance of hyperintense fluid-attenuated inversion-recovery (FLAIR) rim (hyperFLAIRrim) sign for isocitrate dehydrogenase (IDH) mutant 1p/19q non-codeleted (IDHmut-Noncodel) astrocytoma.Methods:A total of 585 lower-grade glioma (LGG) (World Health Organization grade 2-3) patients who received craniotomy at the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from December 2013 to December 2020 were included in this study and their clinical data were retrospectively analyzed. The sensitivity and specificity of T2-FLAIR mismatch and hyperFLAIRrim sign were evaluated. Besides, calcification information was assessed for subgroup analysis. The application value was further determined combined with the calcification information.Results:In 585 qualified patients, 71.3% (186/261)of IDHmut-Noncodel astrocytomas were hyperFLAIRrim positive, and hyperFLAIRrim sign was absent in oligodendrogliomas and IDH wild-type LGGs. The sensitivity for T2-FLAIR mismatch and hyperFLAIRrim sign was 0.52 and 0.71, respectively, and the specificity was 1.00 for both. For all calcific tumors, 85.8% (115/134) were oligodendroglioma. And the sensitivity of T2-FLAIR mismatch and hyperFLAIRrim sign in non-calcific tumors was 0.54 and 0.74, respectively, and the specificity of 1.00 for both.Conclusions:The hyperFLAIRrim sign seems more sensitive for IDHmut-Noncodel astrocytoma without compromised specificity. Combining calcification could further improve the diagnosis sensitivity.

The purpose of this study was to investigate the clinical utility of the sinuous, wave-like intratumoral-wall (SWITW) sign on T2WI in diagnosing isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (IDHmut-Codel) oligodendrogliomas, for which a relatively conservative resection strategy might be sufficient due to a better response to chemoradiotherapy and favorable prognosis. Imaging data from consecutive adult patients with diffuse lower-grade gliomas (LGGs, histological grades 2–3) in Beijing Tiantan Hospital (December 1, 2013, to October 31, 2021, BTH set, n = 711) and the Cancer Imaging Archive (TCIA) LGGs set (n = 117) were used to develop and validate our findings. Two independent observers assessed the SWITW sign and some well-reported discriminative radiological features to establish a practical diagnostic strategy. The SWITW sign showed satisfying sensitivity (0.684 and 0.722 for BTH and TCIA sets) and specificity (0.938 and 0.914 for BTH and TCIA sets) in defining IDHmut-Codels, and the interobserver agreement was substantial (κ 0.718 and 0.756 for BTH and TCIA sets). Compared to calcification, the SWITW sign improved the sensitivity by 0.28 (0.404 to 0.684) in the BTH set, and 81.0 • The SWITW sign was a sensitive and specific imaging biomarker for IDHmut-Codel oligodendrogliomas. • The SWITW sign was more sensitive than calcification and an integrated strategy could improve diagnostic sensitivity for IDHmut-Codel oligodendrogliomas. • Combining SWITW, calcification, low ADC values, and other discriminative features could make a precise preoperative diagnosis for IDHmut-Codel oligodendrogliomas.

Even very small residual tumors of IDH mutant 1p/19q non-codeleted (IDHmut-Noncodel) astrocytoma could have a significantly negative impact on survival; thus, accurate preoperative diagnosis is of utmost importance to guide aggressive tumor resection strategy for this subtype. This study aimed to diagnose IDHmut-Noncodel from IDH mutant 1p/19q codeleted (IDHmut-Codel) and IDH wild-type gliomas by preoperative MRI and CT to guide surgical plan-making. Consecutive adult patients diagnosed with diffuse lower-grade glioma (LGG, histological grade 2–3) from December 1, 2013 to December 31, 2020, were retrospectively included in this study. Clinical and radiological features were recorded and analyzed. Patients were divided into cohort A and cohort B for training and validation based on the operation date (2:1). A total of 585 patients were included in this study (cohort A, 390; cohort B, 195). The hyperintense FLAIR rim with hypointense core (hyperFLAIRrim) was a more sensitive sign than T2-FLAIR mismatch (T2FM) in defining IDHmut-Noncodel astrocytoma (sensitivity in cohort A: 0.713, 0.539, respectively; in cohort B: 0.713, 0.489, respectively) without compromised specificity (all 1.00). The hyperFLAIRrim, higher rADC, homogenous pattern on T2WI, non-calcification, and younger age were the most important factors associated with IDHmut-Noncodel astrocytoma. Combining these factors, the random forest model showed the best predictive ability. The hyperFLAIRrim sign was a specific and more sensitive sign in diagnosing IDHmut-Noncodel astrocytoma. Combining hyperFLAIRrim, higher rADC, homogenous pattern, non-calcification, and younger age could precisely predict glioma subtype for subsequent surgical plan-making. • A single hyperintense FLAIR rim (hyperFLAIRrim) sign with a hypointense core, regardless of T2 appearance, was more sensitive than T2FM in diagnosing IDHmut-Noncodel astrocytoma with high specificity. • The higher rADC value, homogenous pattern on T2WI, non-calcification, and younger age have a close relationship with IDHmut-Noncodel astrocytoma. • Neurosurgeons should perform a more aggressive resection strategy to prolong survival for radiologically indicated IDHmut-Noncodel astrocytoma. Our study provided a usable, practicable, and reliable protocol for neurosurgeons to make an individualized surgical strategy.

Abstract Object: In contrast with the previous diagnostic strategy, which relied only on histopathologic evidence, the integrated diagnosis of oligodendroglioma based on the 5th edition of World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS 5) criteria requires the codeletion of chromosome arms 1p and 19q and isocitrate dehydrogenase gene (IDH1 or IDH2) mutation (mt). The existing prognostic indicators may not be completely suitable for oligodendroglioma patients based on the new diagnostic criteria. We aimed to identify a prognostic prediction model for oligodendrogliomas based on the WHO CNS5 classification.Methods: We collected 175 glioma samples to investigate significant changes in mRNAs using the Chinese Glioma Genome Atlas (CGGA) database and to establish a prediction model for prognosis by Least Absolute Shrinkage and Selection Operator (LASSO) and Cox logistic analysis.Results: Eighty-eight differentially expressed RNAs (DERNAs) were identified between the long survival group and the short survival group. Seven RNAs were selected to calculate risk scores. Risk level, age and Primary-or-Recurrent Status (PRS) type were used as factors for the prognostic model.Conclusion: An individualized prognostic model for oligodendroglioma patients based on the WHO CNS5 criteria was established. The predictive ability of this model was validated in a validation cohort, which demonstrated its predictive accuracy. In the future, more pathological evidence is needed to support our predictive model to further classify oligodendrogliomas.

目的 探讨混合现实电磁导航技术在神经外科制定术前计划和术中导航的应用价值.方法运用混合现实电磁导航技术为4例神经外科患者进行术前影像资料的三维重建,生成可视化三维混合现实图像,明确病变位置及其周围解剖结构的毗邻关系,规划手术入路实施术中导航,同时应用博医来术中导航系统对混合现实导航结果进行验证.结果 应用混合现实术中神经导航技术可在手术室环境重建病变3D结构并导航病变的位置.混合现实术中神经导航结果与博医来神经导航结果一致.结论 混合现实术中导航技术易于应用且定位准确,可用于神经外科制定手术计划和术中导航.

Aneuploidy is the hallmark of malignancy. Our previous study successfully detected nonhematogenic circulating aneuploidy cells (CACs) in types of gliomas. The current prospective clinical study aims to further precisely subcategorize aneuploid CACs, including CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells, and thoroughly investigate the clinical utilities of these different subtypes of cells. Co-detection and analysis of CTCs and circulating tumor-derived endothelial cells (CTECs) expressing CD133, glial fibrillary acidic protein (GFAP), or epidermal growth factor receptor variant III (EGFR vIII) were performed by integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) in 111 preoperative primary diffuse glioma patients. Aneuploid CACs could be detected in most de novo glioma patients. Among detected CACs, 45.6% were CD31- /CD45- aneuploid CTCs and the remaining 54.4% were CD31+ /CD45- aneuploid CTECs. Positive detection of CTECs significantly correlated with disruption of the blood-brain barrier. The median number of large CTCs (L CTCs, >5 μm, 2) in low-grade glioma (WHO grade 2) was less than high-grade glioma (WHO grades 3 and 4) (3, p = 0.044), but this difference was not observed in small CTCs (S CTCs, ≤5 μm), CTECs or CACs (CTCs + CTECs). The numbers of CTCs, CTECs, or CACs in patients with contrast-enhancing (CE) lesions considerably exceeded that of non-CE lesions (p < 0.05). Receiver operating characteristic curves demonstrated that CD31+ CTECs, especially L CTECs, exhibited a close positive relationship with CE lesions. Survival analysis revealed that the high number of CD31- CTCs could be an adverse factor for compromised progression-free survival and overall survival. Longitudinal surveillance of CD31- CTCs was suitable for evaluating the therapeutic response and for monitoring potential emerging treatment resistance.

One biomarker for a better therapeutic effect of immune checkpoint inhibitors is high expression of checkpoint in tumor microenvironment The purpose of this study is to investigate the expression of immune checkpoints in human glioma microenvironment and peripheral blood mononuclear cells. First, single-cell suspension from 20 fresh high-grade glioma (HGG) specimens were obtained, and analyzed for lymphocyte composition, then six co-inhibitory immune checkpoints were analyzed at the same time. Second, 36 PBMC specimens isolated from HGG blood samples were analyzed for the same items. In GME, there were four distinct subtypes of cells, among them, immune cells accounted for an average of 51.3%. The myeloid cell population (CD11b+) was the most common immune cell identified, accounting for 36.14% on average; the remaining were most CD3+CD4+ and CD3+/CD8-/CD4- T lymphocytes. In these cells, we detected the expression of BTLA, LAG3, Tim-3, CTLA-4, and VISTA on varying degrees. While in PBMCs, the result showed that when compared with healthy volunteers, the proportion of NK cells decreased significantly in HGG samples (p < 0.01). Moreover, the expression of BTLA, LAG3, and Tim-3 in CD45+ immune cells in PBMC was more remarkable in glioma samples. In conclusion, the CD11b+ myeloid cells were the predominant immune cells in GME. Moreover, some immune checkpoints displayed a more remarkable expression on the immune cells in GME. And the profile of checkpoint expression in PBMC was partially consistent with that in GME.

Glioma invading the corpus callosum (CC) accounts for approximately 14% of gliomas and is thought to be more aggressive. However, there is still a lack of studies on the pathogenesis and molecular features of this condition. Here, we examined the occurrence association of CC invasion with respect to patients’ clinical, pathological, and genetic characteristics. First, a cohort of 331 patients was included, with 86 cases (26%) that were diagnosed with invasion glioma. They were all analyzed for basic clinical and pathological characteristics and four routinely tested glioma molecular markers. Second, 29 pairs of patients who underwent deep sequencing of 68 glioma molecular alterations were selected from both groups for in-depth analysis. The results of the first part showed that there was no difference between the two groups in terms of the basic factors in univariate analysis, while in multivariate logistic analysis, WHO grade was the risk factor for CC invasion (p = 0.001). The results of the second part showed that the paired groups had different genetic expression profiles, which highlighted glioma invading the CC as a distinct biological entity. PDGFRA mutation (PDGFRAmut) was present in 9 patients with invasive gliomas (31%), but only in one case (3.4%) in the control group (OR 17.331; 95% CI 1.987–151.156). Our data revealed the clinical, pathological, and genetic characteristics of glioma invading the CC and showed that it may be associated with glioma WHO grade and PDGFRAmut, but not other factors. Thus, the risk signaling pathway may offer potential therapeutic targets for this disease.

Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To date,various promising chemotherapeutic regimens have been trialed for use in GBM; however, temozolomide(TMZ) therapy remains the only first ⁃ line chemotherapeutic option for newly diagnosed GBM. Despitemaximal therapy with surgery and combined concurrent radiotherapy and chemotherapy, and adjuvant TMZtherapy, the median overall survival (OS) remains approximately 14.6 months. Given the failure ofconventional chemotherapeutic strategies in GBM, there has been renewed interest in the role ofimmunotherapy in GBM. Dendritic cells (DC) are immune antigen⁃presenting cell (APC) that play a role inboth the innate and adaptive immune system, thereby making them prime vehicles for immunotherapy viaDC vaccinations in various cancers. There is great enthusiasm surrounding the use of vaccinations for GBMwith multiple ongoing trials. In this review, we summarize the progress, prospects and challenges of DCvaccine in the treatment of GBM. DOI：10.3969/j.issn.1672⁃6731.2020.02.008

Purpose: Epileptic seizures often develop in 40-70 % of glioma patients and have a significant impact on patients' quality of life. Many biomarkers have been suggested to be associated with glioma-related preoperative seizures (GPS). The purpose of the present study was to investigate the possible correlation between GPS and clinicopathological factors and a wide range of glioma-associated molecular markers (GMMs). Methods: First, a retrospective cohort study of 442 patients with glioma was evaluated at the PLA General Hospital. Univariate and multivariate logistic analyses were used to identify basic factors associated with GPS. Second, 40 pairs of cases who underwent deep sequencing of 68 GMMs were selected from both groups for indepth analysis. Results: Of the 442 patients examined in this study, 137 (31 %) had GPS. By analyzing the characteristics of these patients, the results showed that patient age (OR: 0.981, p = 0.037, 95 % CI: 0.964 - 0.999), WHO grade (OR: 0.678, p = 0.008, 95 % CI: 0.509 - 0.903) and IDH mutations (OR: 1.886, p = 0.013, 95 % CI: 1.143-3.11) in patients were associated with the occurrence of GPS. In our cohort, GPS did not differ by sex, tumor location, histopathological subtype, p53 expression, ARTX loss, MGMT gene promotor methylation, TERT promoter mutation, or 1p/19q co-deletion status. The results of the matching study showed that the paired groups had similar genetic expression profiles, and the mutation of these 68 GMMs was not correlated with the occurrence of GPS. Conclusion: The current study updates existing information on GPS and genetic markers in gliomas and explores the correlation of a wide range of GMMs and GPS. These factors may provide insights for developing effective treatment strategies aimed at seizure control.